Search

Angrites originate from the early-formed differentiated angrite parent body. The pristine volcanic angrite D’Orbigny is devoid of brecciation, shock effects, or any evidence of secondary processes and is thus key for studying the early stages of planetary accretion and differentiation. However, chronometers used to establish the formation chronology of angrites (including D’Orbigny) yield discordant ages, either (i) suggesting that secondary processes could have disturbed the apparent formation ages or (ii) being taken as evidence of heterogeneous distribution of ^26 Al in the early solar system. Yet spinel is minimally susceptible to secondary parent body processes and therefore a reliable target for establishing precise ^26 Al– ^26 Mg ages. Here, we present the first in situ ^26 Al– ^26 Mg analyses of spinel and plagioclase in D’Orbigny. Individual mineral assemblages provide distinct ages: olivine–spinel shows a well-defined isochron with an initial Al ratio ([ ^26 Al/ ^27 Al] _i ) of (5.39 ± 0.85) × 10 ^−6 , indicating formation at 2.35 $\tfrac{+0.25}{-0.22}$ Myr after the formation of calcium–aluminum-rich inclusions (CAIs), whereas plagioclase–olivine defines an isochron with [ ^26 Al/ ^27 Al] _i = (7.46 ± 1.87) × 10 ^−7 , implying formation at 4.40 $\tfrac{+0.44}{-0.38}$ Myr after CAIs, consistent with previous MC-ICP-MS studies. This temporal gap can be attributed to secondary processes such as metamorphic or impact-generated diffusion. Thus, D’Orbigny and other angrites do not represent an immaculate anchor for chronometric comparison. This complexity should be considered in future studies, especially when using D’Orbigny as an anchor to discuss the chronology of the early solar system.

Abstract INTRODUCTION Measuring day‐to‐day sleep variability might reveal unstable sleep‐wake cycles reflecting neurodegenerative processes. We evaluated the association between Alzheimer's disease (AD) fluid biomarkers with day‐to‐day sleep variability. METHODS In the PREVENT‐AD cohort, 203 dementia‐free participants (age: 68.3 ± 5.4; 78 males) with a parental history of sporadic AD were tested with actigraphy and fluid biomarkers. Day‐to‐day variability (standard deviations over a week) was assessed for sleep midpoint, duration, efficiency, and nighttime activity count. RESULTS Lower cerebrospinal fluid (CSF) ApoE, higher CSF p‐tau181/amyloid‐β (Aβ)42, and higher plasma p‐tau231/Aβ42 were associated with higher variability of sleep midpoint, sleep duration, and/or activity count. The associations between fluid biomarkers with greater sleep duration variability were especially observed in those that carried the APOE4 allele, mild cognitive impairment converters, or those with gray matter atrophy. DISCUSSION Day‐to‐day sleep variability were associated with biomarkers of AD in at‐risk individuals, suggesting that unstable sleep promotes neurodegeneration or, conversely, that AD neuropathology disrupts sleep‐wake cycles.

BackgroundDegenerative Cervical Myelopathy (DCM) is one of the most common degenerative disorders of cervical spine and sources of cord dysfunction in adults. It usually manifests with neurologic presentations such as loss of dexterity and gait issues. Treatment for moderate and severe cases of DCM is surgical decompression of the region. There are many approaches available for surgical intervention which could be categorized into anterior and posterior based on the side of neck where operation takes place. Additionally, for certain cases the hybridized anterior-posterior combined surgery is indicated. While there are many technical differences between these approaches with each having its own advantages, the complications and safety profiles of them are not fully disclosed. This protocol aims to systematically search for current reports on complications of surgical decompression methods of DCM and pool them for robust evidence generation.MethodSearch will be carried out in PubMed, Scopus, and Cochrane databases for retrospective and prospective surgical series, cohorts, or trials being performed for DCM with at least a sample size of 20 patients. Query strings will be designed to capture reports with details of complications with no year limit. Studies not being original (e.g., review articles, case reports, etc.), not in English, having patients younger than 18-years-old, and not reporting at least one complication will be excluded. Two independent reviewers will review the titles and abstracts for first round of screening. Full text of retrieved studies from previous round will be screened again by the same reviewers. In case of discrepancy, the third senior reviewer will be consulted. Eligible studies will then be examined for data extraction where data will be recorded into standardized form. Cumulative incidence and 95% confidence intervals of complication will be then pooled based on generalized linear mixed models with consideration of approach of surgery as subgroups. Heterogeneity tests will be performed for assessment of risk of bias.DiscussionThis systematic review is aimed at providing practical information for spine surgeons on the rates of complications of different surgical approaches of DCM decompression. Proper decision-making regarding the surgical approach in addition to informing patients could be facilitated through results of this investigation.

The unexpected intersection of rhyolitic magma and retrieval of quenched glass particles at the Iceland Deep Drilling Project-1 geothermal well in 2009 at Krafla, Iceland, provide unprecedented opportunities to characterize the genesis, storage, and behavior of subsurface silicic magma. In this study, we analyzed the complete time series of glass particles retrieved after magma was intersected, in terms of distribution, chemistry, and vesicle textures. Detailed analysis of the particles revealed them to represent bimodal rhyolitic magma compositions and textures. Early-retrieved clear vesicular glass has higher SiO2, crystal, and vesicle contents than later-retrieved dense brown glass. The vesicle size and distribution of the brown glass also reveal several vesicle populations. The glass particles vary in δD from −120‰ to −80‰ and have dissolved water contents spanning 1.3−2 wt%, although the majority of glass particles exhibit a narrower range. Vesicular textures indicate that volatile overpressure release predominantly occurred prior to late-stage magma ascent, and we infer that vesiculation occurred in response to drilling-induced decompression. The textures and chemistry of the rhyolitic glasses are consistent with variable partial melting of host felsite. The drilling recovery sequence indicates that the clear magma (lower degree partial melt) overlays the brown magma (higher degree partial melt). The isotopes and water species support high temperature hydration of these partial melts by a mixed meteoric and magmatic composition fluid. The textural evidence for partial melting and lack of crystallization imply that magma production is ongoing, and the growing magma body thus has a high potential for geothermal energy extraction. In summary, transfer of heat and fluids into felsite triggered variable degrees of felsite partial melting and produced a hydrated rhyolite magma with chemical and textural heterogeneities that were then enhanced by drilling perturbations. Such partial melting could occur extensively in the crust above magma chambers, where complex intrusive systems can form and supply the heat and fluids required to re-melt the host rock. Our findings emphasize the need for higher resolution geophysical monitoring of restless calderas both for hazard assessment and geothermal prospecting. We also provide insight into how shallow silicic magma reacts to drilling, which could be key to future exploration of the use of magma bodies in geothermal energy.

Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer's disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (Aβ) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18-94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant Aβ pathology.

PurposeA substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI) are tau PET-negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET-positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status.MethodsWe included 2338 participants (430 Aβ+ AD dementia, 381 Aβ+ MCI, 370 non-AD, and 1157 CU) who underwent [18F]flortaucipir (n = 1944) or [18F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously established cutoffs. We performed bivariate binary logistic regression models with tau PET status (positive/negative) as dependent variable and age, sex, APOEε4, Aβ status (only in CU and non-AD analyses), MMSE, global white matter hyperintensities (WMH), and AD-signature cortical thickness as predictors. Additionally, we performed multivariable binary logistic regression models to account for all other predictors in the same model.ResultsTau PET positivity in the temporal meta-ROI was 88.6% for AD dementia, 46.5% for MCI, 9.5% for non-AD, and 6.1% for CU. Among Aβ+ participants with AD dementia and MCI, lower age, MMSE score, and AD-signature cortical thickness showed the strongest associations with tau PET positivity. In non-AD and CU participants, presence of Aβ was the strongest predictor of a positive tau PET scan.ConclusionWe identified several demographic, clinical, and neurobiological factors that are important to explain the variance in tau PET retention observed across the AD pathological continuum, non-AD neurodegenerative disorders, and cognitively unimpaired persons.

Age is the greatest risk factor for Parkinson's disease (PD) which causes progressive loss of dopamine (DA) neurons, with males at greater risk than females. Intriguingly, some DA neurons are more resilient to degeneration than others. Increasing evidence suggests that vesicular glutamate transporter (VGLUT) expression in DA neurons plays a role in this selective vulnerability. We investigated the role of DA neuron VGLUT in sex- and age-related differences in DA neuron vulnerability using the genetically tractable Drosophila model. We found sex differences in age-related DA neurodegeneration and its associated locomotor behavior, where males exhibit significantly greater decreases in both DA neuron number and locomotion during aging compared with females. We discovered that dynamic changes in DA neuron VGLUT expression mediate these age- and sex-related differences, as a potential compensatory mechanism for diminished DA neurotransmission during aging. Importantly, female Drosophila possess higher levels of VGLUT expression in DA neurons compared with males, and this finding is conserved across flies, rodents, and humans. Moreover, we showed that diminishing VGLUT expression in DA neurons eliminates females' greater resilience to DA neuron loss across aging. This offers a new mechanism for sex differences in selective DA neuron vulnerability to age-related DA neurodegeneration. Finally, in mice, we showed that the ability of DA neurons to achieve optimal control over VGLUT expression is essential for DA neuron survival. These findings lay the groundwork for the manipulation of DA neuron VGLUT expression as a novel therapeutic strategy to boost DA neuron resilience to age- and PD-related neurodegeneration.

Arbuscular mycorrhizal fungi (AMF) (subphylum Glomeromycotina)1 are among the most prominent symbionts and form the Arbuscular Mycorrhizal symbiosis (AMS) with over 70% of known land plants.2,3 AMS allows plants to efficiently acquire poorly soluble soil nutrients4 and AMF to receive photosynthetically fixed carbohydrates. This plant-fungus symbiosis dates back more than 400 million years5 and is thought to be one of the key innovations that allowed the colonization of lands by plants.6 Genomic and genetic analyses of diverse plant species started to reveal the molecular mechanisms that allowed the evolution of this symbiosis on the host side, but how and when AMS abilities emerged in AMF remain elusive. Comparative phylogenomics could be used to understand the evolution of AMS.7,8 However, the availability of genome data covering basal AMF phylogenetic nodes (Archaeosporales, Paraglomerales) is presently based on fragmentary protein coding datasets.9Geosiphon pyriformis (Archaeosporales) is the only fungus known to produce endosymbiosis with nitrogen-fixing cyanobacteria (Nostoc punctiforme) presumably representing the ancestral AMF state.10-12 Unlike other AMF, it forms long fungal cells ("bladders") that enclose cyanobacteria. Once in the bladder, the cyanobacteria are photosynthetically active and fix nitrogen, receiving inorganic nutrients and water from the fungus. Arguably, G. pyriformis represents an ideal candidate to investigate the origin of AMS and the emergence of a unique endosymbiosis. Here, we aimed to advance knowledge in these questions by sequencing the genome of G. pyriformis, using a re-discovered isolate.

The bigmouth buffalo (Ictiobus cyprinellus) is an iconic freshwater fish native to North America that is in decline. Recent studies have revealed bigmouth buffalo exhibit a slow pace of life, yet demographic information on bigmouth buffalo outside of North Dakota and Minnesota is lacking. We used otoliths to investigate population demographics of bigmouth buffalo in Canada, and also monitored bigmouth buffalo spawning frequency and reproductive success in the wild. From a sample of 52 fish collected during 2018-2021 we found bigmouth buffalo from the Qu'Appelle system more than 125 years old. Only 13 year classes ranging from 1894-1997 were evident with one year class since 1948, indicating recruitment has been episodic. During the past decade (2013-2022) bigmouth buffalo have spawned only once (May 2013) in Buffalo Pound Lake. This spawning effort culminated in recruitment failure because the water-level recession rate was too rapid. Our findings indicate that bigmouth buffalo spawning attempts as well as recruitment occur within a narrow range of water-level fluctuations that may rarely occur, which is enabled by their supercentenarian lifespan, and has direct implications for the conservation of this species. Key words: supercentenarians, otoliths, Qu'Appelle, episodic recruitment, buffalofish, Introduction Bigmouth buffalo (Ictiobus cyprinellus) is a freshwater fish native to North America that is in decline, and as a result is increasingly gaining attention and study. It is the [...]

Abstract Prior research has demonstrated the importance of a healthy lifestyle to protect brain health and diminish dementia risk in later life. While a multidomain lifestyle provides an ecological perspective to voluntary engagement, its association with brain health is still under-investigated. Therefore, understanding the neural mechanisms underlying multidomain lifestyle engagement, particularly in older adults at risk for Alzheimer’s disease (AD), gives valuable insights into providing lifestyle advice and intervention for those in need. The current study included 139 healthy older adults with familial risk for AD from the Prevent-AD longitudinal aging cohort. Self-reported exercise engagement, cognitive activity engagement, healthy diet adherence, and social activity engagement were included to examine potential phenotypes of an individual’s lifestyle adherence. Two adherence profiles were discovered using data-driven clustering methodology [i.e., Adherence to healthy lifestyle (AL) group and Non-adherence to healthy lifestyle group]. Resting-state functional connectivity matrices and grey matter brain features obtained from magnetic resonance imaging were used to classify the two groups using a support vector machine (SVM). The SVM classifier was 75% accurate in separating groups. The features that show consistently high importance to the classification model were functional connectivity mainly between nodes located in different prior-defined functional networks. Most nodes were located in the default mode network, dorsal attention network, and visual network. Our results provide preliminary evidence of neurobiological characteristics underlying multidomain healthy lifestyle choices.

Abstract Background This study compares the outcome of patients suffering from medically refractory classical trigeminal neuralgia (TN) after treatment with radiosurgery using two different shot sizes (5- and 6-mm). Methods All patients included in this open, prospective, non-controlled study were treated in a single institution for TN (95 cases in 93 patients) with LINear ACcelerators (LINAC) single-dose radiosurgery using a 5-mm shot (43 cases) or 6-mm shot (52 cases). The target was positioned on the intracisternal part of the trigeminal nerve. Results The mean Dmax (D0.035) to the brainstem was higher in the 6-mm group: 12.6 vs 21.3 Gy (p 25 Gy (20 cases). At 12 months the rates of hypoesthesia were 11.3, 33.5 and 76.0%, respectively in groups 1, 2 and 3 (p

New therapies in a publicly funded healthcare system are first appraised by health technology assessment agencies that provide funding recommendations to the payers. Treatment with Chimeric Antigen Receptor-T cell (CAR-T) therapy is revolutionizing the management of patients with relapsed/refractory aggressive B-cell lymphoma by providing an effective alternative to the standard of care. Yet, the implementation of CAR-T treatment has a substantial impact on the healthcare system due to its high cost, complex manufacturing process, and requirement for highly specialized services and expertise. CAR-T Cells, as a “living drug”, are fundamentally different from usual medications, and their approvals and funding recommendations pose unique challenges to the health technology agency. In this paper, we explore the specific challenges that face the health technology agencies in reviewing reimbursement recommendations for CAR-T therapy. We take a Canadian perspective and use CAR-T treatment of relapse/refractory aggressive B-cell lymphoma as an example.

Abstract Background The medial parietal cortex is an early site of pathological protein deposition in Alzheimer’s disease (AD). Previous studies have identified different subregions within this area; however, these subregions are often heterogeneous and disregard individual differences or subtle pathological alterations in the underlying functional architecture. To address this limitation, here we measured the continuous connectivity gradients of the medial parietal cortex and assessed their relationship with cerebrospinal fluid (CSF) biomarkers, ApoE ε4 carriership and memory in asymptomatic individuals at risk to develop AD. Methods Two hundred sixty-three cognitively normal participants with a family history of sporadic AD who underwent resting-state and task-based functional MRI using encoding and retrieval tasks were included from the PREVENT-AD cohort. A novel method for characterizing spatially continuous patterns of functional connectivity was applied to estimate functional gradients in the medial parietal cortex during the resting-state and task-based conditions. This resulted in a set of nine parameters that described the appearance of the gradient across different spatial directions. We performed correlation analyses to assess whether these parameters were associated with CSF biomarkers of phosphorylated tau181 (p-tau), total tau (t-tau), and amyloid-ß1-42 (Aß). Then, we compared the spatial parameters between ApoE ε4 carriers and noncarriers, and evaluated the relationship between these parameters and memory. Results Alterations involving the superior part of the medial parietal cortex, which was connected to regions of the default mode network, were associated with higher p-tau, t-tau levels as well as lower Aß/p-tau levels during the resting-state condition (p

IntroductionIn adults, chronic exposure to air pollution is associated with elevated blood pressure, but few studies have examined this relationship in youth. We investigated the association between annual ambient concentrations of air pollutants (fine particulate matter [PM2.5] and nitrogen dioxide [NO2]) and systolic blood pressure (SBP) among adolescents in Montréal, Canada. MethodsParticipants were students aged 15 to 17 years who provided SBP and residential postal code data in 2004/05 through their enrolment in the Nicotine Dependence in Teens study. Annual estimates for 2004 of residential exposure to NO2 and PM2.5 were provided by the Canadian Urban Environmental Health Research Consortium and linked to participants’ residential postal code. Elevated SBP was defined as SBP ≥ 90th percentile adjusted for age, sex and height. Logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for each pollutant with respect to elevated SBP, adjusted for relevant confounders. ResultsThe sample consisted of 508 adolescents (mean age: 16.9, 46% male); 4% had elevated SBP. Although estimates were not statistically significant, there were generally modest positive associations between pollutant levels and SBP. The adjusted prevalence odds ratio of elevated SBP was 1.33 (95% CI: 0.64, 3.05) for every interquartile range (IQR) increase in residential PM2.5 levels (2.1μg/m3). Similarly, the adjusted prevalence odds ratio of elevated SBP was 1.17 (95% CI: 0.47, 2.70) for every IQR increase in residential NO2 levels (10.2 ppb). ConclusionFindings support a possible relationship between exposure to air pollutants and increased SBP in adolescents, warranting further investigation for this important public health concern.

IntroductionChez l’adulte, l’exposition chronique à la pollution atmosphérique est associée à une élévation de la pression artérielle, mais peu d’études ont porté sur ce lien chez les jeunes. Nous avons étudié l’association entre les concentrations ambiantes annuelles de polluants atmosphériques (particules fines [PM2,5] et dioxyde d’azote [NO2]) et la pression artérielle systolique (PAS) chez des adolescents à Montréal (Canada). MéthodologieLes participants étaient des élèves de 15 à 17 ans ayant fourni des données sur leur PAS et le code postal de leur lieu de résidence en 2004-2005 dans le cadre de l’étude sur la dépendance à la nicotine chez les adolescents (NICO). Les estimations annuelles de l’exposition résidentielle au NO2 et aux PM2,5 pour 2004, fournies par le Canadian Urban Environmental Health Research Consortium, ont été couplées au code postal du lieu de résidence des participants. La PAS a été jugée élevée lorsqu’elle était supérieure ou égale au 90e percentile ajusté pour l’âge, le sexe et la taille. Une régression logistique a servi à estimer les rapports de cotes et les intervalles de confiance (IC) à 95 % pour l’association entre chaque polluant et une PAS élevée, avec ajustement pour les variables de confusion pertinentes. RésultatsL’échantillon comprenait 508 adolescents (âge moyen : 16,9 ans; 46 % étant de sexe masculin), dont 4 % avec une PAS élevée. Même si les estimations ne sont pas statistiquement significatives, des associations positives généralement modestes ont été constatées entre les concentrations de polluants et la PAS. Le rapport de cotes ajusté de la prévalence d’une PAS élevée était de 1,33 (IC à 95 % : 0,64 à 3,05) par augmentation de chaque intervalle interquartile (IIQ) de concentration résidentielle de PM2,5 (2,1 μg/m3). De même, le rapport de cotes ajusté de la prévalence d’une PAS élevée était de 1,17 (IC à 95 % : 0,47 à 2,70) par augmentation de chaque IIQ de concentration résidentielle de NO2 (10,2 ppb). ConclusionLes résultats corroborent l’existence d’un lien possible entre l’exposition aux polluants atmosphériques et l’élévation de la PAS chez les adolescents, ce qui justifie une analyse approfondie portant sur cet important problème de santé publique.

Abstract Senior housing for older adults could be an alternative or a transitional care model between home care and nursing home care. Using two longitudinal cohorts of community dwellers aged 65 years or older, we compared risks of mortality and of nursing homes admission between older adults who did or did not move to senior housing over time. In the 3C study (n = 2104, 17 years of follow-up), 143 (6.8%) participants moved into a senior housing during the follow-up. This move was associated with a lower risk of mortality (hazard ratio (HR): 0.64; 95% confidence interval (CI) 0.46–0.77) and a higher risk of nursing home admissions (HR: 1.54 (1.10–2.15)). The risks of hospitalizations (HR: 0.54 (0.40–0.73)) and falls (HR: 0.63 (0.50–0.79)) were lower. In the PAQUID study (n = 3777, 27 years of follow-up), 161 (4.3%) participants moved into a senior housing. This move was also associated with a lower mortality risk (HR: 0.72 (0.58–0.88)) and a higher risk of nursing home admissions (HR: 1.39 (1.05–1.86)). Our results showing lower risks of mortality suggest that senior housing may be a relevant model for vulnerable older adults.

RationaleThe mechanisms underlying atrial fibrillation (AF), the most common clinical arrhythmia, are poorly understood. Nucleoplasmic Ca2+ regulates gene expression, but the nature and significance of nuclear Ca2+-changes in AF are largely unknown.ObjectiveTo elucidate mechanisms by which AF alters atrial-cardiomyocyte nuclear Ca2+ ([Ca2+]Nuc) and CaMKII (Ca2+/calmodulin-dependent protein kinase-II)-related signaling.Methods and resultsAtrial cardiomyocytes were isolated from control and AF dogs (kept in AF by atrial tachypacing [600 bpm × 1 week]). [Ca2+]Nuc and cytosolic [Ca2+] ([Ca2+]Cyto) were recorded via confocal microscopy. Diastolic [Ca2+]Nuc was greater than [Ca2+]Cyto under control conditions, while resting [Ca2+]Nuc was similar to [Ca2+]Cyto; both diastolic and resting [Ca2+]Nuc increased with AF. IP3R (Inositol-trisphosphate receptor) stimulation produced larger [Ca2+]Nuc increases in AF versus control cardiomyocytes, and IP3R-blockade suppressed the AF-related [Ca2+]Nuc differences. AF upregulated nuclear protein expression of IP3R1 (IP3R-type 1) and of phosphorylated CaMKII (immunohistochemistry and immunoblot) while decreasing the nuclear/cytosolic expression ratio for HDAC4 (histone deacetylase type-4). Isolated atrial cardiomyocytes tachypaced at 3 Hz for 24 hours mimicked AF-type [Ca2+]Nuc changes and L-type calcium current decreases versus 1-Hz-paced cardiomyocytes; these changes were prevented by IP3R knockdown with short-interfering RNA directed against IP3R1. Nuclear/cytosolic HDAC4 expression ratio was decreased by 3-Hz pacing, while nuclear CaMKII phosphorylation was increased. Either CaMKII-inhibition (by autocamtide-2-related peptide) or IP3R-knockdown prevented the CaMKII-hyperphosphorylation and nuclear-to-cytosolic HDAC4 shift caused by 3-Hz pacing. In human atrial cardiomyocytes from AF patients, nuclear IP3R1-expression was significantly increased, with decreased nuclear/nonnuclear HDAC4 ratio. MicroRNA-26a was predicted to target ITPR1 (confirmed by luciferase assay) and was downregulated in AF atrial cardiomyocytes; microRNA-26a silencing reproduced AF-induced IP3R1 upregulation and nuclear diastolic Ca2+-loading.ConclusionsAF increases atrial-cardiomyocyte nucleoplasmic [Ca2+] by IP3R1-upregulation involving miR-26a, leading to enhanced IP3R1-CaMKII-HDAC4 signaling and L-type calcium current downregulation. Graphic Abstract: A graphic abstract is available for this article.